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Artikel ; Online: The innate immune response following multivalent dengue vaccination and implications for protection against dengue challenge

Ruixue Hou / Lewis E. Tomalin / Jessica Pintado Silva / Seunghee Kim-Schulze / Stephen S. Whitehead / Ana Fernandez-Sesma / Anna P. Durbin / Mayte Suárez-Fariñas

JCI Insight, Vol 7, Iss

2022 Band 11

Abstract: Understanding the immune response to dengue virus (DENV) is essential for developing a dengue vaccine that is protective against all 4 DENV serotypes. We evaluated the immune response after vaccination (live attenuated tetravalent dengue vaccine TV005 or ...

Abstract	Understanding the immune response to dengue virus (DENV) is essential for developing a dengue vaccine that is protective against all 4 DENV serotypes. We evaluated the immune response after vaccination (live attenuated tetravalent dengue vaccine TV005 or trivalent admixture) and after challenge with DEN2Δ30 (Tonga/74) to better understand the importance of homotypic immunity in vaccine protection. Significant increases in IP-10 expression were observed following receipt of either the trivalent or tetravalent vaccine. After challenge, a large increase in IP-10 expression was observed in the placebo and trivalent admixture groups but not in the tetravalent vaccine group. MCP-1, IL-1RA, and MIP-1β exhibited a similar pattern as IP-10. These results demonstrate protective effects of trivalent and tetravalent vaccines against DENV and suggest that the tetravalent vaccine has a better protective effect compared with the trivalent admixture. We also explored the postvaccination and postchallenge immune response differences between Black and White participants. White participants responded to vaccine differently than Black participants; Black participants receiving trivalent and tetravalent vaccines responded strongly and White participants responded only transiently in trivalent group. In response to challenge, White participants elicited a stronger response than Black participants. These results may explain why White participants may have a more vigorous DENV immune response than Black participants, as reported in literature.
Schlagwörter	Immunology ; Infectious disease ; Medicine ; R
Thema/Rubrik (Code)	150
Sprache	Englisch
Erscheinungsdatum	2022-06-01T00:00:00Z
Verlag	American Society for Clinical investigation
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Randomized trial of a portable HEPA air cleaner intervention to reduce asthma morbidity among Latino children in an agricultural community

Rebecca L. Drieling / Paul D. Sampson / Jennifer E. Krenz / Maria I. Tchong French / Karen L. Jansen / Anne E. Massey / Stephanie A. Farquhar / Esther Min / Adriana Perez / Anne M. Riederer / Elizabeth Torres / Lisa R. Younglove / Eugene Aisenberg / Syam S. Andra / Seunghee Kim-Schulze / Catherine J. Karr

Environmental Health, Vol 21, Iss 1, Pp 1-

2022 Band 16

Abstract: Abstract Background Data on pediatric asthma morbidity and effective environmental interventions in U.S. agricultural settings are few. We evaluated the effectiveness of HEPA air cleaners on asthma morbidity among a cohort of rural Latino children. ... ...

Abstract	Abstract Background Data on pediatric asthma morbidity and effective environmental interventions in U.S. agricultural settings are few. We evaluated the effectiveness of HEPA air cleaners on asthma morbidity among a cohort of rural Latino children. Methods Seventy-five children with poorly controlled asthma and living in non-smoking homes were randomly assigned to asthma education alone or along with HEPA air cleaners placed in their sleeping area and home living room. The Asthma Control Test (ACT) score, asthma symptoms in prior 2 weeks, unplanned clinical utilization, creatinine-adjusted urinary leukotriene E4 (uLTE4 [ng/mg]), and additional secondary outcomes were evaluated at baseline, six, and 12 months. Group differences were assessed using multivariable-adjusted generalized estimating equations. Incident rate ratios of ever experiencing the metrics of poorer asthma health during follow-up (suboptimal asthma management) were estimated using Poisson regression models in secondary analysis. Results Mean child age was 9.2 and 8.6 years in intervention and control groups, respectively, and two-thirds of participants were male. Primary analysis of repeated measures of ACT score did not differ between groups (HEPA group mean change compared to controls 10% [95% CI: − 12-39%]). A suggestion of greater decrease in uLTE4 (ng/mg creatinine) was observed (− 10% [95% CI: − 20 -1%]). Secondary analysis showed children with HEPAs were less likely to have an ACT score meeting a clinically defined cutoff for poorly controlled asthma using repeated measures (IRR: 0.45 [95% CI: 0.21–0.97]). In Poisson models, intervention participants had reduced risk of ever meeting this cutoff (IRR: 0.43 [95% CI: 0.21–0.89]), ever having symptoms in the past 2 weeks (IRR: 0.71 [95% CI: 0.52–0.98]), and lower risk of any unplanned clinical utilization (IRR: 0.35 [95% CI: 0.13–0.94]) compared to control participants. Discussion The HAPI study showed generally improved outcomes among children in the HEPA air cleaner group. However, primary ...
Schlagwörter	Air pollution ; Childhood asthma ; HEPA air cleaner ; Randomized controlled trial ; Industrial medicine. Industrial hygiene ; RC963-969 ; Public aspects of medicine ; RA1-1270
Thema/Rubrik (Code)	610
Sprache	Englisch
Erscheinungsdatum	2022-01-01T00:00:00Z
Verlag	BMC
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Cross center single-cell RNA sequencing study of the immune microenvironment in rapid progressing multiple myeloma

npj Genomic Medicine, Vol 8, Iss 1, Pp 1-

2023 Band 18

Abstract: Abstract Despite advancements in understanding the pathophysiology of Multiple Myeloma (MM), the cause of rapid progressing disease in a subset of patients is still unclear. MM’s progression is facilitated by complex interactions with the surrounding ... ...

Abstract	Abstract Despite advancements in understanding the pathophysiology of Multiple Myeloma (MM), the cause of rapid progressing disease in a subset of patients is still unclear. MM’s progression is facilitated by complex interactions with the surrounding bone marrow (BM) cells, forming a microenvironment that supports tumor growth and drug resistance. Understanding the immune microenvironment is key to identifying factors that promote rapid progression of MM. To accomplish this, we performed a multi-center single-cell RNA sequencing (scRNA-seq) study on 102,207 cells from 48 CD138- BM samples collected at the time of disease diagnosis from 18 patients with either rapid progressing (progression-free survival (PFS) < 18 months) or non-progressing (PFS > 4 years) disease. Comparative analysis of data from three centers demonstrated similar transcriptome profiles and cell type distributions, indicating subtle technical variation in scRNA-seq, opening avenues for an expanded multicenter trial. Rapid progressors depicted significantly higher enrichment of GZMK + and TIGIT + exhausted CD8+ T-cells (P = 0.022) along with decreased expression of cytolytic markers (PRF1, GZMB, GNLY). We also observed a significantly higher enrichment of M2 tolerogenic macrophages in rapid progressors and activation of pro-proliferative signaling pathways, such as BAFF, CCL, and IL16. On the other hand, non-progressive patients depicted higher enrichment for immature B Cells (i.e., Pre/Pro B cells), with elevated expression for markers of B cell development (IGLL1, SOX4, DNTT). This multi-center study identifies the enrichment of various pro-tumorigenic cell populations and pathways in those with rapid progressing disease and further validates the robustness of scRNA-seq data generated at different study centers.
Schlagwörter	Medicine ; R ; Genetics ; QH426-470
Thema/Rubrik (Code)	610
Sprache	Englisch
Erscheinungsdatum	2023-01-01T00:00:00Z
Verlag	Nature Portfolio
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: A methylation clock model of mild SARS‐CoV‐2 infection provides insight into immune dysregulation

Weiguang Mao / Clare M Miller / Venugopalan D Nair / Yongchao Ge / Mary Anne S Amper / Antonio Cappuccio / Mary‐Catherine George / Carl W Goforth / Kristy Guevara / Nada Marjanovic / German Nudelman / Hanna Pincas / Irene Ramos / Rachel S G Sealfon / Alessandra Soares‐Schanoski / Sindhu Vangeti / Mital Vasoya / Dawn L Weir / Elena Zaslavsky /

Biobank Team / Seunghee Kim‐Schulze / Sacha Gnjatic / Miriam Merad / Andrew G Letizia / Olga G Troyanskaya / Stuart C Sealfon / Maria Chikina

Molecular Systems Biology, Vol 19, Iss 5, Pp n/a-n/a (2023)

2023

Abstract: Abstract DNA methylation comprises a cumulative record of lifetime exposures superimposed on genetically determined markers. Little is known about methylation dynamics in humans following an acute perturbation, such as infection. We characterized the ... ...

Abstract	Abstract DNA methylation comprises a cumulative record of lifetime exposures superimposed on genetically determined markers. Little is known about methylation dynamics in humans following an acute perturbation, such as infection. We characterized the temporal trajectory of blood epigenetic remodeling in 133 participants in a prospective study of young adults before, during, and after asymptomatic and mildly symptomatic SARS‐CoV‐2 infection. The differential methylation caused by asymptomatic or mildly symptomatic infections was indistinguishable. While differential gene expression largely returned to baseline levels after the virus became undetectable, some differentially methylated sites persisted for months of follow‐up, with a pattern resembling autoimmune or inflammatory disease. We leveraged these responses to construct methylation‐based machine learning models that distinguished samples from pre‐, during‐, and postinfection time periods, and quantitatively predicted the time since infection. The clinical trajectory in the young adults and in a diverse cohort with more severe outcomes was predicted by the similarity of methylation before or early after SARS‐CoV‐2 infection to the model‐defined postinfection state. Unlike the phenomenon of trained immunity, the postacute SARS‐CoV‐2 epigenetic landscape we identify is antiprotective.
Schlagwörter	DNA methylation ; machine learning model ; SARS‐CoV‐2 ; temporal dynamics ; trained immunity ; Biology (General) ; QH301-705.5 ; Medicine (General) ; R5-920
Thema/Rubrik (Code)	570
Sprache	Englisch
Erscheinungsdatum	2023-05-01T00:00:00Z
Verlag	Wiley
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Comprehensive Immunoprofiling of Pediatric Zika Reveals Key Role for Monocytes in the Acute Phase and No Effect of Prior Dengue Virus Infection

Daniela Michlmayr / Eun-Young Kim / Adeeb H. Rahman / Rohit Raghunathan / Seunghee Kim-Schulze / Yan Che / Selim Kalayci / Zeynep H. Gümüş / Guillermina Kuan / Angel Balmaseda / Andrew Kasarskis / Steven M. Wolinsky / Mayte Suaréz-Fariñas / Eva Harris

Cell Reports, Vol 31, Iss 4, Pp - (2020)

2020

Abstract: Summary: Zika virus (ZIKV) is an emerging, mosquito-borne flavivirus responsible for recent epidemics across the Americas, and it is closely related to dengue virus (DENV). Here, we study samples from 46 DENV-naive and 43 DENV-immune patients with RT-PCR- ...

Abstract	Summary: Zika virus (ZIKV) is an emerging, mosquito-borne flavivirus responsible for recent epidemics across the Americas, and it is closely related to dengue virus (DENV). Here, we study samples from 46 DENV-naive and 43 DENV-immune patients with RT-PCR-confirmed ZIKV infection at early-acute, late-acute, and convalescent time points from our pediatric cohort study in Nicaragua. We analyze the samples via RNA sequencing (RNA-seq), CyTOF, and multiplex cytokine/chemokine Luminex to generate a comprehensive, innate immune profile during ZIKV infection. Immunophenotyping and analysis of cytokines/chemokines reveal that CD14+ monocytes play a key role during ZIKV infection. Further, we identify CD169 (Siglec-1) on CD14+ monocytes as a potential biomarker of acute ZIKV infection. Strikingly distinct transcriptomic and immunophenotypic signatures are observed at all three time points. Interestingly, pre-existing dengue immunity has minimal impact on the innate immune response to Zika. Finally, this comprehensive immune profiling and network analysis of ZIKV infection in children serves as a valuable resource. : At three time points after Zika virus infection, Michlmayr et al. perform comprehensive immunoprofiling of pediatric cohort samples via RNA-seq, CyTOF, and Luminex cytokine/chemokine array, resulting in distinct temporal patterns of gene expression, cell profiles, and cytokines/chemokines. They show CD14+ monocytes play a central role, identify CD169 as a potential biomarker of acute ZIKV infection along with upregulation of CXCL10, and find no impact of prior dengue virus infection on the innate immune response to Zika. Keywords: Zika virus, monocytes, dengue virus, innate immunity, immune profiling, RNA-seq, CyTOF, network model, biomarker, Luminex
Schlagwörter	Biology (General) ; QH301-705.5
Thema/Rubrik (Code)	570
Sprache	Englisch
Erscheinungsdatum	2020-04-01T00:00:00Z
Verlag	Elsevier
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes

Al Ozonoff / Naresh Doni Jayavelu / Shanshan Liu / Esther Melamed / Carly E. Milliren / Jingjing Qi / Linda N. Geng / Grace A. McComsey / Charles B. Cairns / Lindsey R. Baden / Joanna Schaenman / Albert C. Shaw / Hady Samaha / Vicki Seyfert-Margolis / Florian Krammer / Lindsey B. Rosen / Hanno Steen / Caitlin Syphurs / Ravi Dandekar /

Casey P. Shannon / Rafick P. Sekaly / Lauren I. R. Ehrlich / David B. Corry / Farrah Kheradmand / Mark A. Atkinson / Scott C. Brakenridge / Nelson I. Agudelo Higuita / Jordan P. Metcalf / Catherine L. Hough / William B. Messer / Bali Pulendran / Kari C. Nadeau / Mark M. Davis / Ana Fernandez Sesma / Viviana Simon / Harm van Bakel / Seunghee Kim-Schulze / David A. Hafler / Ofer Levy / Monica Kraft / Chris Bime / Elias K. Haddad / Carolyn S. Calfee / David J. Erle / Charles R. Langelier / Walter Eckalbar / Steven E. Bosinger / IMPACC Network / Bjoern Peters / Steven H. Kleinstein / Elaine F. Reed / Alison D. Augustine / Joann Diray-Arce / Holden T. Maecker / Matthew C. Altman / Ruth R. Montgomery / Patrice M. Becker / Nadine Rouphael

Nature Communications, Vol 15, Iss 1, Pp 1-

results from the IMPACC study

2024 Band 17

Abstract: Abstract Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. ... ...

Abstract	Abstract Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B lymphocytes by mass cytometry (CyTOF) was observed in the multidomain deficit cluster. Circulating fibroblast growth factor 21 (FGF21) was significantly elevated in the mental/cognitive predominant and the multidomain clusters. Future efforts to link PASC to acute anti-viral host responses may help to better target treatment and prevention of PASC.
Schlagwörter	Science ; Q
Sprache	Englisch
Erscheinungsdatum	2024-01-01T00:00:00Z
Verlag	Nature Portfolio
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Length of gestation and birth weight are associated with indices of combined kidney biomarkers in early childhood.

Yuri Levin-Schwartz / Paul Curtin / Katherine Svensson / Nicolas F Fernandez / Seunghee Kim-Schulze / Gleicy M Hair / Daniel Flores / Ivan Pantic / Marcela Tamayo-Ortiz / María Luisa Pizano-Zárate / Chris Gennings / Lisa M Satlin / Andrea A Baccarelli / Martha M Tellez-Rojo / Robert O Wright / Alison P Sanders

PLoS ONE, Vol 14, Iss 12, p e

2019 Band 0227219

Abstract: Infants born prematurely or with low birth weights are more susceptible to kidney dysfunction throughout their lives. Multiple proteins measured in urine are noninvasive biomarkers of subclinical kidney damage, but few studies have examined the joint ... ...

Abstract	Infants born prematurely or with low birth weights are more susceptible to kidney dysfunction throughout their lives. Multiple proteins measured in urine are noninvasive biomarkers of subclinical kidney damage, but few studies have examined the joint effects of multiple biomarkers. We conducted an exploratory study of 103 children in the Programing Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) longitudinal birth cohort, and measured nine proteins selected a priori in banked spot urine samples collected at ages 4-6. The goal of our study was to explore the combined effects of kidney damage biomarkers previously associated with birth outcomes. To do this, we generated kidney biomarker indices using weighted quantile sum regression and assessed associations with length of gestation or birth weight. A decile increase in each kidney biomarker index was associated with 2-day shorter gestations (β = -2.0, 95% CI: -3.2, -0.9) and 59-gram lower birth weights (β = -58.5, 95% CI: -98.3, -18.7), respectively. Weights highlighting the contributions showed neutrophil gelatinase-associated lipocalin (NGAL) (60%) and osteopontin (19%) contributed most to the index derived for gestational age. NGAL (66%) and beta-2-microglobulin (10%) contributed most to the index derived for birth weight. Joint analyses of multiple kidney biomarkers can provide integrated measures of kidney dysfunction and improved statistical assessments compared to biomarkers assessed individually. Additionally, shorter gestations and lower birth weights may contribute to subclinical kidney damage measurable in childhood.
Schlagwörter	Medicine ; R ; Science ; Q
Thema/Rubrik (Code)	616
Sprache	Englisch
Erscheinungsdatum	2019-01-01T00:00:00Z
Verlag	Public Library of Science (PLoS)
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Gut microbiota density influences host physiology and is shaped by host and microbial factors

Eduardo J Contijoch / Graham J Britton / Chao Yang / Ilaria Mogno / Zhihua Li / Ruby Ng / Sean R Llewellyn / Sheela Hira / Crystal Johnson / Keren M Rabinowitz / Revital Barkan / Iris Dotan / Robert P Hirten / Shih-Chen Fu / Yuying Luo / Nancy Yang / Tramy Luong / Philippe R Labrias / Sergio Lira /

Inga Peter / Ari Grinspan / Jose C Clemente / Roman Kosoy / Seunghee Kim-Schulze / Xiaochen Qin / Anabella Castillo / Amanda Hurley / Ashish Atreja / Jason Rogers / Farah Fasihuddin / Merjona Saliaj / Amy Nolan / Pamela Reyes-Mercedes / Carina Rodriguez / Sarah Aly / Kenneth Santa-Cruz / Lauren Peters / Mayte Suárez-Fariñas / Ruiqi Huang / Ke Hao / Jun Zhu / Bin Zhang / Bojan Losic / Haritz Irizar / Won-Min Song / Antonio Di Narzo / Wenhui Wang / Benjamin L Cohen / Christopher DiMaio / David Greenwald

eLife, Vol

2019 Band 8

Abstract: To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic ... ...

Abstract	To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohn’s disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between microbiota and disease in terms of microbiota density, host carrying capacity, and microbiota fitness provide new insights into microbiome structure and microbiome targeted therapeutics.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
Schlagwörter	gut microbiome ; microbiota density ; inflammatory bowel disease ; fecal microbiota transplantation ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Sprache	Englisch
Erscheinungsdatum	2019-01-01T00:00:00Z
Verlag	eLife Sciences Publications Ltd
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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